Research Interests

Publications

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Research Abstract

All eukaryotic cells tightly control cellular pH. Proper control of cytoplasmic pH is essential for normal metabolism and cell growth, and acidification of organelles such as the lysosome, endosome, and Golgi apparatus is essential for protein sorting and degradation, ion homeostasis, and signal transduction. The vacuolar ATPase (V-ATPase) is one of the central players in pH control. All eukaryotic cells have V-ATPases of remarkably similar structure, and loss of V-ATPase function is lethal at early stages of development in higher eukaryotes and conditionally lethal in fungi.

The yeast V-ATPase has proven to be an excellent model for studies of V-ATPase structure, function, and regulation. Work in my laboratory addresses three major questions using yeast as a model system: 1) definition of functional and structural relationships among the fourteen subunits of the V-ATPase
2) regulation of the V-ATPase in vivo, 3) physiological implications of organelle acidification. We approach these questions using a combination of biochemical, genetic, molecular, and cell biological methods. Our studies of subunit structure and function combine traditional biochemistry and yeast genetics with insights from the growing number of complete eukaryotic genomes now available. Regulation of V-ATPases is proving to be rich and complex. Assembled V-ATPases can rapidly and reversibly dissociate in vivo in response to changes in growth conditions, and this appears to be a major regulatory mechanism. Current work is directed toward defining this signal transduction pathway and probing the possibility of crosstalk between V-ATPase regulation and other pathways and processes. Finally, V-ATPases are implicated in a number of unexpected roles, including resistance to oxidative stress. We seek to better understand these rolls and their links to overall cellular pH control.